FOXS1 Promotes Tumor Progression by Upregulating CXCL8 in Colorectal Cancer

Qiu, Jun-Feng; Li, Mingzhou; Su, Cailin; Liang, Yi-Hao; Ou, Ruizhang; Chen, Xiaoning; Huang, Chengmei; Zhang, Yaxin; Ye, Yaping; Liao, Wenting; Zhang, Chao

doi:10.3389/fonc.2022.894043

Cited by 9 publications

(5 citation statements)

References 54 publications

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“…DNA sites near FOXF1 and FOXL1 genes contain GLI binding consensus and both genes are targets of the GLI family, an effect that was confirmed when GLI2/GLI3 mutations reduced the expression of FOXF1 and FOXL1 ( Madison et al, 2009 ). FOXS1 upregulated the mRNA abundance of CXCL8 (C-X-C Motif Chemokine Ligand 8; also known as IL-8), which is a key signal for neutrophil activation in colorectal cancer ( Qiu et al, 2022 ). Overall, the known connections among the GLI/GLIS with the FOXF/FOXL reported in previous studies along with the present data suggest a potential functional link in the ileum.…”

Section: Resultsmentioning

confidence: 99%

Alterations in ileal transcriptomics during an intestinal barrier challenge in lactating Holstein cows fed a Saccharomyces cerevisiae fermentation product identify potential regulatory processes

Jiang,

Palombo,

Sherlock

et al. 2023

Journal of Animal Science

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Stressors such as lack of access to feed, hot temperatures, transportation, and pen changes can cause impairment of ruminal and intestinal barrier function, also known as "leaky gut". Despite the known benefits of some nutritional approaches during periods of stress, little is understood regarding the underlying mechanisms, especially in dairy cows. We evaluated the effect of feeding a Saccharomyces cerevisiae fermentation product (SCFP; NutriTek®, Diamond V, Cedar Rapids, IA) on the ileal transcriptome in response to feed restriction (FR), an established model to induce intestinal barrier dysfunction. Multiparous cows (97.1 ± 7.6 DIM; n = 5/group) fed a control diet or control plus 19 g/d SCFP for 9 wk were subjected to an FR challenge for 5-d during which they were fed 40% of their ad-libitum intake from the 7 d before FR. All cows were slaughtered at the end of FR, and ileal scrapping RNA was used for RNAseq (NovaSeq 6000, 100 bp read length). Statistical analysis was performed in R and bioinformatics using the KEGG and GO databases. One thousand six hundred and ninety-six differentially-expressed genes (DEG; FDR-adjusted P ≤ 0.10) were detected in SCFP versus control, with 451 upregulated and 1,245 downregulated. “Mucin type O-glycan biosynthesis” was the top downregulated KEGG pathway due to downregulation of genes catalyzing glycosylation of mucins (GCNT3, GALNT5, B3GNT3, GALNT18, and GALNT14). An overall downregulation of cell and tissue structure genes (e.g., extracellular matrix proteins) associated with collagen (COL6A1, COL1A1, COL4A1, COL1A2, COL6A2), laminin (LAMB2), and integrins (ITGA8, ITGA2, ITGA5) also were detected with SCFP. A subset of DEG enriched in the GO term “extracellular exosome” and “extracellular space”. Chemokines within “Cytokine-cytokine receptor interaction pathways” such as CCL16, CCL21, CCL14, CXCL12, and CXCL14 were downregulated by SCFP. The “Glutathione metabolism” pathway was upregulated by SCFP, including GSTA1 and RRM2B among the top upregulated genes, and GSTM1 and GPX8 as top downregulated genes. There were 9 homeobox transcription factors among the top 50 predicted transcription factors using the RNAseq DEG dataset, underscoring the importance of cell differentiation as a potential target of dietary SCFP. Taken together, SCFP downregulated immune-, ECM-, and mucin synthesis-related genes during FR. Homeobox transcription factors appear important for the transcriptional response of SCFP.

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Section: Resultsmentioning

confidence: 99%

Alterations in ileal transcriptomics during an intestinal barrier challenge in lactating Holstein cows fed a Saccharomyces cerevisiae fermentation product identify potential regulatory processes

Jiang,

Palombo,

Sherlock

et al. 2023

Journal of Animal Science

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“…Furthermore, it has been observed that FOXS1 is silenced in the majority of non‐tumor tissues 17 . The role of the FOXS1/CXCL8 axis in facilitating cancer cell migration, invasion, angiogenesis, as well as metastasis in CRC has been recognized, indicating the possibility of targeting this axis as a viable approach to inhibit tumor‐associated angiogenesis and effectively manage advanced CRC 11 . However, the specific role of FOXS1 in the onset and progress of human malignancies remains extensively unexplored, and there is still an ongoing debate regarding its involvement in cancer.…”

Section: Discussionmentioning

confidence: 99%

“…17 The role of the FOXS1/CXCL8 axis in facilitating cancer cell migration, invasion, angiogenesis, as well as metastasis in CRC has been recognized, indicating the possibility of targeting this axis as a viable approach to inhibit tumorassociated angiogenesis and effectively manage advanced CRC. 11 However, the specific role of FOXS1 in the onset and progress of human malignancies remains extensively unexplored, and there is still an ongoing debate regarding its involvement in cancer. For instance, Lu et al 18 observed a downregulation of FOXS1 expression in gastric cancer, while its overexpression effectively suppressed the growth, metastasis, and EMT process in gastric malignancy cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…8,9 Previous study has indicated a strong link between FOXS1 and gastric cancer, with evidence suggesting that it has a function in promoting cell growth and facilitating the epithelialmesenchymal transition (EMT) process within this type of cancer. 10 Qiu et al 11 suggested that the enhancement of CXCL8 expression mediated by FOXS1 could have a function in facilitating angiogenesis and metastasis in colorectal cancer (CRC). Additionally, Zhang et al 12 reported FOXS1 has the potential to act as an oncogene, promoting the growth, movement, infiltration, and dissemination of CRC cells through the activation of the Wnt/β-catenin pathway.…”

Section: Introductionmentioning

confidence: 99%

“…Previous study has indicated a strong link between FOXS1 and gastric cancer, with evidence suggesting that it has a function in promoting cell growth and facilitating the epithelial–mesenchymal transition (EMT) process within this type of cancer 10 . Qiu et al 11 . suggested that the enhancement of CXCL8 expression mediated by FOXS1 could have a function in facilitating angiogenesis and metastasis in colorectal cancer (CRC).…”

Section: Introductionmentioning

confidence: 99%

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FOXS1 acts as an oncogene and induces EMT through FAK/PI3K/AKT pathway by upregulating HILPDA in prostate cancer

Ren,

Wang,

et al. 2024

The FASEB Journal

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Prostate cancer (PCa) is a widespread global health concern characterized by elevated rates of occurrence, and there is a need for novel therapeutic targets to enhance patient outcomes. FOXS1 is closely linked to different cancers, but its function in PCa is still unknown. The expression of FOXS1, its prognostic role, clinical significance in PCa, and the potential mechanism by which FOXS1 affects PCa progression were investigated through bioinformatics analysis utilizing public data. The levels of FOXS1 and HILPDA were evaluated in clinical PCa samples using various methods, such as western blotting, immunohistochemistry, and qRT‐PCR. To examine the function and molecular mechanisms of FOXS1 in PCa, a combination of experimental techniques including CCK‐8 assay, flow cytometry, wound‐healing assay, Transwell assay, and Co‐IP assay were employed. The FOXS1 expression levels were significantly raised in PCa, correlating strongly with tumor aggressiveness and an unfavorable prognosis. Regulating FOXS1 expression, whether upregulating or downregulating it, correspondingly enhanced or inhibited the growth, migration, and invasion capabilities of PCa cells. Mechanistically, we detected a direct interaction between FOXS1 and HILPDA, resulting in the pathway activation of FAK/PI3K/AKT and facilitation EMT in PCa cells. FOXS1 collaborates with HILPDA to initiate EMT, thereby facilitating the PCa progression through the FAK/PI3K/AKT pathway activation.

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Comprehensive scRNA-seq Model Reveals Artery Endothelial Cell Heterogeneity and Metabolic Preference in Human Vascular Disease

Zeng,

Liu,

et al. 2023

Interdiscip Sci Comput Life Sci

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FOXS1 Promotes Tumor Progression by Upregulating CXCL8 in Colorectal Cancer

Cited by 9 publications

References 54 publications

Alterations in ileal transcriptomics during an intestinal barrier challenge in lactating Holstein cows fed a Saccharomyces cerevisiae fermentation product identify potential regulatory processes

Alterations in ileal transcriptomics during an intestinal barrier challenge in lactating Holstein cows fed a Saccharomyces cerevisiae fermentation product identify potential regulatory processes

FOXS1 acts as an oncogene and induces EMT through FAK/PI3K/AKT pathway by upregulating HILPDA in prostate cancer

Comprehensive scRNA-seq Model Reveals Artery Endothelial Cell Heterogeneity and Metabolic Preference in Human Vascular Disease

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